Cancer Mortality Among Populations Exposed to Radioactive Waste in the Techa River by Mayak Nuclear Facility Cancer mortality is being evaluated in a cohort of approximately 30,000 people who lived by the banks of the Techa River in the Southern Urals of Russia and had protracted environmental radiation exposure from radioactive waste released into the river by the Mayak nuclear facility. Current efforts focus on statistical analyses using the recent follow-up data and dosimetry system and manuscript preparation. Significant dose-response relationships have been observed for both solid cancer and leukemia mortality. Chernobyl Thyroid Study in Belarus/Ukraine /b The Chernobyl accident in Ukraine contaminated large parts of Belarus, northwestern Ukraine, and bordering Russian provinces. Two case-control studies with individual dose estimates demonstrated a statistically significant link between thyroid cancer and environmental radiation dose from fallout related to the accident. REB and collaborators organized follow-up screening studies of benign and malignant thyroid disease among those exposed as children to fallout from the accident in Belarus and in Ukraine. The thyroid glands of approximately 12,000 subjects in each country have been screened biennially for four cycles in Ukraine and three cycles in Belarus. The projects have transitioned from active screening to other forms of follow-up using existing national cancer registries. Cohort-based GWAS of Glioma We have almost completed a cohort-based genome wide association study of glioma including 18 studies from the Cohort Consortium, with the aim of confirming gene regions associated with glioma risk, identifying new regions of genetic susceptibility that may be more apparent in a cohort setting, and conducting targeted gene-environment analyses based on the covariate data available from cohorts. Development of Computer Program for Organ Dose Calculations The computer program is based on Monte Carlo transport technique coupled with computational human phantoms to provide organ dose estimates for individuals exposed to radiological accidents or terrorist events. Dose reconstruction and Health Effects of In-utero and Early Life Radiation Exposure Appropriate medical countermeasures for prevention of adverse health effects following radiological or nuclear incidents are critical to radiation protection of exposed populations, and are of particular scientific, medical and public concern when pregnant women and their offspring are involved. Several thousands of children born in Belarus during the period from April 26, 1986 through February 28, 1987, were exposed in utero and in early life as a result of the Chernobyl accident. This study will establish a cohort of about 2,500 Belarusian individuals exposed in utero and in early life to radioactive iodine and other radioactive isotopes from Chernobyl fallout, reconstruct doses to the thyroid gland from internal and external radiation exposure, ascertain thyroid cancer and other thyroid diseases and assess radiation dose-responses. NHANES III: Prospective Vitamin Study The NHANES III data set with measured vitamin D levels on about 20,000 people is a resource that allows investigation of the relationship between vitamin D and specific causes of mortality. This cohort includes actual vitamin D measurements and about 2253 deaths, of which nearly 900 are cancer deaths. The dataset also allows examination of relationships between vitamin D and other circulating hormones (e.g., testosterone), which may contribute to cancer associations. Nordic Brain Collaboration Analyses from the NCI Adult Brain Tumor Study have identified possible risk factors for brain tumors including environmental factors such as exposure to lead, and genetic factors, including polymorphisms involved in lead metabolism. We plan to test these hypotheses using data from Nordic case-control studies of adult brain tumors for replication studies. Telomere Length and Risk of Glioma Recently published genome wide association studies of glioma indicate that the TERT gene, which codes for thr enzyme telomerase reverse transcriptase, is likely to be important in glioma etiology. We will examine the association between telomere length and the risk of glioma, and will explore whether telomere length variation is modified by TERT polymorphisms that are highly associated with glioma risk. Skin Cancer in Radiologic Technologists Exposure to ultraviolet (UV) radiation from sunlight plays a predominant role in the etiology of melanoma and non-melanoma skin cancer, but the nature of the relationship is not fully understood. We recently completed questionnaire-based collection of lifetime UV sun-related radiation exposure from more than 70,000 U.S. radiologic technologists and have undertaken analyses to assess risks of specific forms of cancer in relation to exposure. We also plan to evaluate whether skin cancer risks associated with occupational exposures to ionizing radiation might be modified by questionnaire-derived estimates of UV radiation exposures. UV Exposure and Colorectal Adenomas in Fernald Community Cohort The Fernald Community cohort includes data on UV radiation exposure over time and colorectal adenomas identified by medical procedures. This study aims at examing the association between personal UV radiation exposure over time and colorectal adenoma incidence. Study to Improve Thyroid Doses from Fallout Exposure in Kazakhstan This builds on an existing study of radiation exposure and thyroid disease among individuals in Kazakhstan exposed during childhood to radioactive fallout from nuclear tests conducted at the Semipalatinsk Nuclear Test Site between 1949 and 1962. High thyroid doses to this population from both internal and external radiation sources present a unique opportunity to quantify and compare the two types as risk factors for thyroid disease in a single population. A field study using focus group interviews has been conducted to investigate aspects of typical village life in areas affected by fallout that might influence individual radiation doses to the thyroid gland. We collected retrospective information about factors influencing radiation dose to the thyroid gland in children of two distinct ethnic groups, including milk and milk product consumption, seasonal practices of pasturing and supplemental feeding of dairy animals at the time of the nuclear tests, time spent outdoors, and radiation shielding provided by buildings. These data will fill key gaps in the current dose-reconstruction methodology and should result in improved dose estimates, providing the basis for evaluating and quantifying dosimetric uncertainty and related biases in risk estimates. Thyroid Cancer Genetic Consortium (THYGENE) We plan to perform a GWAS of differentiated thyroid cancer using 4,000 cases from several studies in THYGENE (including radiologic technologists studies) and 10,000 controls amassed from control series of other large studies, with replication in 1500 thyroid cancer cases and controls by remaining THYGENE consortium member. These studies include ionizing radiation and non-radiation-exposed subjects.